This group works on gene regulation in the immune system. Our focus has been to elucidate the role of two transcription factors, RXRbeta and ICSBP. RXRbeta is a member of the large nuclear hormone receptor superfamily. It heterodimerizes with other receptors and regulates ligand dependent transcription. ICSBP is a member of the interferon regulatory factor (IRF) family and regulates expression of interferon and interferon inducible genes. To address the mechanisms by which the RXR heterodimers and IRF proteins regulate transcription, several approaches are taken to identify factors that interact with them. We found that TFIIB, a component of the basal transcription complex, interact with the RXR heterodimer as well as proteins of the IRF family, and that the interaction results in transcriptional stimulation. Our results indicate that DNA binding transcription factors can directly interact with the basal transcription complex, which may leads to stabilization of the pre-initiation complex. We have also found that RXR heterodimers and IRF proteins interact with enzymes that modulate levels of histone acetylation. Particularly interesting is the finding that the histone acetylase PCAF is recruited to the RXR/RAR heterodimer that had been bound to the DNA in a ligand dependent manner. Recruitment of PCAF may contribute to ligand induced alteration of chromatin structure in the RARbeta promoter,stimulated by RXR heterodimers, observed in an independent work. Similarly, PCAF recruitment was detected by IRF-1 and IRF-2 also bound to the specific DNA element. Evidence by reporter analyses indicates that recruitment of PCAF by these transcription factors results in transcriptional enhancement, which in turn modulate biological effects of ligands and cytokines. To elucidate the in vivo role of ICSBP, host defense against pathogens was investigated in ICSBP-/-mice by using a parasite infection model. ICSBP-/- mice are found to be highly susceptible to Toxolasma gondii, and die soon after infection. By testing cytokine gene expression in various immune cells we found that ICSBP-/- mice fail to induce IL-12 gene transcription, which leads to the severe deficiency in interferon _ production and the subsequent immune responses. These studies thus revealed a previously unidentified cytokine-interferon connections, in which ICSBP takes a critical part.